Evaluation of a model for brain bilirubin uptake in jaundiced newborns

Area of Science:

• Neonatal Medicine
• Biochemistry
• Pharmacokinetics

Background:

• Jaundice in newborns involves bilirubin accumulation.
• Brain bilirubin uptake (BBU) models are crucial for understanding neonatal neurotoxicity.
• Previous models suggested BBU depends on plasma total bilirubin concentration (TBC) and dissociation rate (k1).

Purpose of the Study:

• To test the validity of a BBU model predicting dependence on TBC and k1.
• To evaluate the model's requirement that k3>>>k2 (rate constants for BBU and unbound bilirubin-albumin association).
• To determine if calculated BBU aligns with expected low brain bilirubin levels (<1% of the miscible bilirubin pool).

Main Methods:

• Investigated 185 jaundiced newborns using peroxidase tests.
• Measured plasma total bilirubin concentration (TBC), unbound bilirubin (Bf), and rate constants k1 and k2.
• Calculated BBU using TBC/k1 and compared it with Bf-based calculations and bilirubin production rate.

Main Results:

• Mean k2 (8.9 L/micromol/s) was greater than k3 (0.08/s), contradicting the model's assumption.
• BBU calculated from TBC and k1 (0.72 microg/kg/s) exceeded the expected range (
• BBU calculated from Bf (0.00073 microg/kg/s) was within the expected range and consistent with literature.

Conclusions:

• The mathematical model predicting BBU as a function of TBC and k1 could not be validated.
• BBU calculated using unbound bilirubin (Bf) is consistent with low brain bilirubin distribution in jaundiced newborns.
• Unbound bilirubin (Bf) is a more critical determinant of brain bilirubin uptake than previously modeled.